HIV-infected people can have an increase in inflammation in their body organs, even after taking anti-HIV medicines.

Sevelamer carbonate is used to bind phosphate in dialysis patients. It can also bind endotoxin in the gut and lowers endotoxin levels in the blood of dialysis patients. Sevelamer carbonate decreases the inflammation endotoxin causes in dialysis patients.

A5296 is a phase II, single-arm study to evaluate the effect of 8 weeks of sevelamer carbonate administration on markers of microbial translocation and T-cell activation in the blood in chronically HIV-infected subjects not receiving ART.

Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks.

Drug: Sevelamer carbonate

Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks.

Other Name: Renvela

Device: Sevelamer carbonate

Other Name: Renvela

Detailed Description:

HIV-infected people can have an increase in inflammation in their body organs, even after taking anti-HIV medicines. Inflammation is a normal body reaction to any infection. However, if inflammation lasts a long time like in HIV infection, it may lead to complications, such as heart disease, cancer, liver disease, and problems with thinking. Also, HIV-infected people with high inflammation have lower CD4+ T-cell counts (cells that fight infection). Many HIV researchers are studying the harmful effects of this prolonged inflammation and possible ways to prevent these complications.

The increase in inflammation in HIV-infected people may be caused by HIV or by other factors such as parts of bacteria. These bacterial pieces, called endotoxins, do not cause harm in the intestine (gut). However, in HIV infection, there is damage to the gut that allows endotoxins to cross from the gut into the blood. These endotoxins then cause inflammation in the body. New research is focusing on strategies to reduce the levels of endotoxin as a way to decrease inflammation.

A drug called sevelamer carbonate is used to bind phosphate in dialysis patients. However, sevelamer carbonate also binds endotoxin in the gut and lowers endotoxin levels in the blood of dialysis patients. Sevelamer carbonate also decreases the inflammation endotoxin causes in dialysis patients. This study will see if sevelamer carbonate can have the same effects in HIV-infected patients.

A5296 is a phase II, single-arm study to evaluate the effect of 8 weeks of sevelamer carbonate administration on markers of microbial translocation as well as monocyte and T-cell activation in the blood in chronically HIV-infected subjects with CD4+ T-cell count ≥ 400 cells/mm3 not receiving ART. This study enrolled 40 subjects. To assess whether there is a persistent effect of study drug, subjects were observed for an additional 8 weeks off sevelamer carbonate and changes in biomarkers were monitored.

As A5296 is a phase II study of biologic activity, the primary and secondary analyses are as-treated, limited to subjects who have data for baseline and week 8 and who remain on study treatment through week 8. For any subject who initiated antiretroviral treatment (ART), analyses only included data collected prior to the time ART was started.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

HIV-1 infection

No plans to initiate ART during the course of the proposed study.

Screening CD4+ T-cell count ≥ 400 cells/mm3 performed in a laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.

HIV-1 RNA >50 copies/mL within the last 180 days prior to entry.

Screening serum phosphate > 2.6 mg/dL within 60 days prior to entry.

Certain laboratory values, as detailed in section 4.1.6 of the protocol, obtained within 30 days prior to entry

Female subjects of reproductive potential must have a negative serum or urine pregnancy test performed within 30 days prior to entry.

Female subjects participating in sexual activity that could lead to pregnancy must agree to use at least one of the following forms of birth control for at least 30 days prior to study entry until the final study visit:

Condoms (male or female) with or without a spermicidal agent

Diaphragm or cervical cap with spermicide

Intrauterine device (IUD)

Hormone-based contraceptive

Female subjects who are not of reproductive potential are eligible without requiring the use of a contraceptive.

Confirmation of the availability of the stored pre-entry plasma and peripheral blood mononuclear cell (PBMC) samples for endotoxin, sCD14, and immune activation determinations, obtained from a fasting sample.

Ability and willingness of subject to provide informed consent.

No plans to use probiotics (defined as products that contain significant amounts of live microorganisms and are ingested for specific health benefits, e.g., yogurt with live and active cultures, Lactobacillus GG, Saccharomyces boulardii) during the study.

Exclusion Criteria:

Known diagnosis of acute HIV infection within 180 days prior to study entry.

History of bowel obstruction or severe GI motility disorders including severe constipation.

Severe dysphagia or swallowing disorders.

Major GI tract surgery within 60 days prior to study entry.

Intent to initiate or change the dose of lipid-lowering drugs during study. NOTE: Potential subjects on stable doses of lipid-lowering agents (defined as no change in preparation or dose within 90 days prior to study entry) are permitted and may be enrolled.

Use of investigational therapies within 90 days prior to study entry unless permission was granted by the A5296 protocol chairs (see Study Management page).

Currently receiving hepatitis C therapy or anticipation that such therapy will be started during the study.

Use of probiotics, for more than 3 consecutive days within the 60 days prior to study entry.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01543958